Altered proteasome function and subunit composition in aged muscle

Arch Biochem Biophys. 2004 Jan 1;421(1):67-76. doi: 10.1016/


Myofibrillar protein degradation is mediated through the ubiquitin-proteasome pathway. To investigate if altered proteasome activity plays a role in age-related muscle atrophy, we examined muscle size and proteasome function in young and aged F344BN rats. Significant age-related muscle atrophy was confirmed by the 38% decrease in cross-sectional area of type 1 fibers in soleus muscle. Determination of proteasome function showed hydrolysis of fluorogenic peptides was equivalent between ages. However, when accounting for the 3-fold increase in content of the 20S catalytic core in aged muscle, the lower specific activity suggests a functional loss in individual proteins with aging. Comparing the composition of the catalytic beta-subunits showed an age-related 4-fold increase in the cytokine-inducible subunits, LMP2 and LMP7. Additionally, the content of the activating complexes, PA28 and PA700, relative to the 20S proteasome was reduced 50%. These results suggest significant alterations in the intrinsic activity, the percentage of immunoproteasome, and the regulation of the 20S proteasome by PA28 and PA700 in aged muscle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Atrophy / metabolism
  • Binding Sites
  • Cell Cycle Proteins
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cytokines / metabolism
  • Hydrolysis
  • In Vitro Techniques
  • Kinetics
  • Leupeptins / pharmacology
  • Male
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / metabolism*
  • Muscle Proteins / analysis
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Proteasome Endopeptidase Complex
  • Protein Biosynthesis
  • Protein Subunits
  • Proteins / analysis
  • Rats
  • Rats, Inbred F344
  • Up-Regulation


  • Cell Cycle Proteins
  • Cysteine Proteinase Inhibitors
  • Cytokines
  • Leupeptins
  • Multienzyme Complexes
  • Muscle Proteins
  • Oligopeptides
  • PA700 proteasome activator
  • Protein Subunits
  • Proteins
  • Psme1 protein, rat
  • Psme2 protein, rat
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde